This project is a continuation from last year. Its aim is to test in rhesus macaques the potency of various live vectors carrying human immunodeficiency virus type 1 (HIV-1), HIV-2 and simian immunodeficiency virus (SIV) antigens in eliciting a protective immunoresponse. Three different delivery systems have been tested: 1) attenuated vaccinia, 2) avipox, and 3) attenuated Salmonella typhimurium strain as a bacterial vaccine, carrying HIV/SIV antigens. The immunoresponse in the immunized animals will be further stimulated by using purified viral antigens (either native or recombinant viral subunits). Rhesus macaques, which are susceptible to the infection of both SIV(mac251) and HIV-2, will be used. The end point of these studies will be the protection from infection by either SIV or HIV-2. Vectors containing HIV-1 antigens will also be evaluated for their immunogenicity in rhesus macaques. The animals immunized with SIV/HIV-2 recombinant vectors have been challenged with live virus twice at six months apart. The results indicate that NYVAC recombinant vaccines are better immunogens than ALVAC and recombinant Salmonella and provide long lasting protection without need of further boosts. Another aspect of prevention of viral infection has been investigated using phosphorothioated oligonucleotides against HIV-1 auxillary genes (vpr and vif). Further information on the biological importance of the HIV-2 auxillary genes in vitro and in vivo has also been obtained.